Summary of Work: As the number of persons infected with Human Immunodeficiency Virus (HIV) reaches 2 million in the United States, there is growing concern among occupational groups such as health care workers, first responders, sanitation workers, police and firemen that they may become infected with HIV through accidental needlesticks or splashes occurring at work. Nucleoside analogues such as Zidovudine (also referred to as AZT) are offered as prophylaxis to occupational groups following exposure to HIV contaminated materials. Use of dideoxynucleosides, such as ZDV, in healthy populations for prophylaxis has not been examined for potential reproductive or long term mutagenic effects. Such investigation is warranted given that genetic damage in humans and genetic plus reproductive effects have been reported in animals exposed to ZDV, and the data obtained would be of help to individuals and their physicians in making more informed risk/benefit decisions about the use of this type of prophylaxis following accidental occupational exposures. A cohort study comparing individuals occupationally exposed to HIV who elect to take ZDV or other dideoxynucleoside prophylaxis therapy to a similar occupationally exposed group individuals who do not elect this prophylaxis therapy is being conducted. Cytogenetic effects in blood lymphocytes, and both fertility and cytogenetic parameters in sperm, are being evaluated (repeated measures design) for individuals preparing to start dideoxynucleoside therapy, and pre- , during, and post- dideoxynucleoside therapy. Subjects are being recruited from occupational exposures to HIV occurring in the greater Triangle area during a two year period and referred to the Clinical Research Study sites for specimen collection. Additionally, semen from HIV infected individuals preparing to start dideoxynucleoside therapy, and pre- , during, and post- dideoxynucleoside therapy, are also being evaluated for cytogenetic and fertility effects. During the past year, IRB approvals were obtained from all of the participating hospitals and NIEHS, the Task Order Contracts were finalized with both UNC and Duke, and 3 HIV-positive patients were enrolled in the study with blood samples processed though our contract with Genetics Res. Inc. Due to a delay in finalizing the contracts with the UNC and Duke Fertility Clinics, sperm samples on only one of these 3 patients have been processed to date. Epidemiological questionnaires have been completed on each of the patients.